Under this grant several studies now underway will be pursued in the Hematology Research Laboratory at Cleveland Metropolitan General Hospital all basically related to erythrocyte production and destruction. Intermediate stages in the sol-gel transformation of deoxygenated S Hb will be characterized by continuous monitoring of viscosity, electron microscopy, and laser light scattering to define polymer forms. Monkeys, made severely deficient in vitamin B12 alone by dietary manipulations and manifesting combined degeneration of spinal cord, brain, and optic tracts will be sacrificed for neuropathological studies by light and electron microscopy (in vivo fixation by perfusion), for biochemical studies concerning enzyme systems dependent upon B12, and for biochemical studies relative to the hematopoietic tissues and the nervous system. Studies will be continued on the sideroblastic anemias (B6 responsive and non-responsive) relative to the interrelationships of B6, PLP, PLK, tryptophan and mitochondrial iron metabolism. BIBLIOGRAPHIC REFERENCES: Brittenham, G., Lozoff, B., Harris, J.W., Hussman, T.H.J. and Sastry, D.B.: Non-duplication of alpha-chain genes in S. Indians, an explanation for decreased alpha-chain synthesis and low % Hbs in heterozygotes. Clin Research 24: 437A, 1976. Bukowski, R.M., Hewlett, J.S., Harris, J.W., Hoffman, G.C., Battle, J.D., Silverblatt, E. and I-Yen Yang. Exchange transknowns in the treatment of thrombotic thrombocytopenic purpura. Seminars in Hematol 13: 219, 1976.